SitesBLAST
Comparing BWI76_RS14160 FitnessBrowser__Koxy:BWI76_RS14160 to proteins with known functional sites using BLASTp with E ≤ 0.001.
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Found 20 (the maximum) hits to proteins with known functional sites (download)
P35486 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial; PDHE1-A type I; EC 1.2.4.1 from Mus musculus (Mouse) (see 2 papers)
37% identity, 99% coverage: 2:319/320 of query aligns to 55:371/390 of P35486
- S232 (≠ G181) modified: Phosphoserine; by PDK1
- S293 (≠ F244) modified: Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
- S300 (vs. gap) modified: Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
- K336 (≠ A284) modified: N6-acetyllysine; mutation K->Q,R: Decreases phosphorylation at S-232 and S-300 but does not affect activity or substrate metabolism.
P29803 Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial; PDHE1-A type II; EC 1.2.4.1 from Homo sapiens (Human) (see 4 papers)
37% identity, 99% coverage: 2:319/320 of query aligns to 53:369/388 of P29803
- M227 (≠ E178) to V: in SPGF70; uncertain significance; dbSNP:rs200969445
- S230 (≠ G181) mutation to A: Slightly reduces enzyme activity.
- S291 (≠ F244) modified: Phosphoserine; by PDK1, PDK2, PDK3 and PDK4; mutation to A: Strongly reduces enzyme activity. Increases enzyme activity in stem cells.; mutation S->E,D: Abolishes enzyme activity. Increases neuronal cell death in response to glutamate excitotoxicity.
- S293 (≠ G246) modified: Phosphoserine; mutation to A: Increases enzyme activity in stem cells.; mutation to D: Abolishes enzyme activity. Increases neuronal cell death in response to glutamate excitotoxicity.
- S298 (vs. gap) modified: Phosphoserine; by PDK3; mutation to A: Slightly reduces enzyme activity.
P26284 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial; PDHE1-A type I; EC 1.2.4.1 from Rattus norvegicus (Rat) (see paper)
37% identity, 99% coverage: 2:319/320 of query aligns to 55:371/390 of P26284
- S232 (≠ G181) modified: Phosphoserine; by PDK1
- S293 (≠ F244) modified: Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
- S300 (vs. gap) modified: Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
P08559 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial; PDHE1-A type I; EC 1.2.4.1 from Homo sapiens (Human) (see 13 papers)
37% identity, 99% coverage: 2:319/320 of query aligns to 55:371/390 of P08559
- A136 (= A83) to T: found in a patient with moderate developmental delay, mild dysmorphism and mildly elevated serum lactate; uncertain significance; dbSNP:rs138727886
- S232 (≠ G181) modified: Phosphoserine; by PDK1; mutation to A: Abolishes inactivation by phosphorylation; when associated with A-293 and A-300.
- M282 (≠ I233) to L: in dbSNP:rs2229137
- S293 (≠ F244) modified: Phosphoserine; by PDK1, PDK2, PDK3 and PDK4; mutation to A: Reduces enzyme activity. Abolishes inactivation by phosphorylation; when associated with A-232 and A-300.; mutation to E: Interferes with substrate binding.
- S300 (vs. gap) modified: Phosphoserine; by PDK1, PDK2, PDK3 and PDK4; mutation to A: Abolishes inactivation by phosphorylation; when associated with A-232 and A-293.
- R302 (= R252) to C: in PDHAD; loss of activity; common mutation; dbSNP:rs137853252
Sites not aligning to the query:
- 1:29 modified: transit peptide, Mitochondrion
- 10 R → P: in PDHAD; affects mitochondrial import of precursor protein; dbSNP:rs137853257
6cfoA Human pyruvate dehydrogenase e1 component complex with covalent tdp adduct acetyl phosphinate (see paper)
37% identity, 99% coverage: 2:319/320 of query aligns to 27:343/362 of 6cfoA
- active site: Q52 (= Q27), G137 (≠ A114), R260 (= R239), H264 (= H243), S265 (≠ F244), Y273 (= Y251)
- binding 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-2-{(1S)-1-hydroxy-1-[(R)-hydroxy(oxo)-lambda~5~-phosphanyl]ethyl}-5-(2-{[(S)-hydroxy(phosphonooxy)phosphoryl]oxy}ethyl)-4-methyl-1,3-thiazol-3-ium: F62 (= F37), Y90 (≠ H65), R91 (= R66), G137 (≠ A114), V139 (= V116), G167 (= G144), D168 (= D145), G169 (= G146), N197 (= N174), Y199 (= Y176), G200 (= G177), H264 (= H243)
- binding magnesium ion: D168 (= D145), N197 (= N174), Y199 (= Y176)
1ni4A Human pyruvate dehydrogenase (see paper)
37% identity, 99% coverage: 2:319/320 of query aligns to 27:343/362 of 1ni4A
- active site: Q52 (= Q27), G137 (≠ A114), R260 (= R239), H264 (= H243), S265 (≠ F244), Y273 (= Y251)
- binding magnesium ion: D168 (= D145), N197 (= N174), Y199 (= Y176)
- binding thiamine diphosphate: Y90 (≠ H65), R91 (= R66), V139 (= V116), G167 (= G144), D168 (= D145), G169 (= G146), A170 (≠ G147), N197 (= N174), G200 (= G177), H264 (= H243)
3exeA Crystal structure of the pyruvate dehydrogenase (e1p) component of human pyruvate dehydrogenase complex (see paper)
37% identity, 99% coverage: 2:319/320 of query aligns to 28:344/363 of 3exeA
- active site: Q53 (= Q27), G138 (≠ A114), R261 (= R239), H265 (= H243), S266 (≠ F244), Y274 (= Y251)
- binding manganese (ii) ion: D169 (= D145), N198 (= N174), Y200 (= Y176)
- binding thiamine diphosphate: Y91 (≠ H65), R92 (= R66), V140 (= V116), G168 (= G144), D169 (= D145), G170 (= G146), A171 (≠ G147), N198 (= N174), Y200 (= Y176), G201 (= G177), H265 (= H243)
P16387 Pyruvate dehydrogenase E1 component subunit alpha, mitochondrial; Pyruvate dehydrogenase complex component E1 alpha; PDHE1-A; EC 1.2.4.1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) (see 2 papers)
37% identity, 98% coverage: 4:318/320 of query aligns to 77:392/420 of P16387
- S313 (≠ F244) modified: Phosphoserine; by PDK1 and PDK2
Sites not aligning to the query:
- 1:33 modified: transit peptide, Mitochondrion
Q10489 Pyruvate dehydrogenase E1 component subunit alpha, mitochondrial; PDHE1-A; EC 1.2.4.1 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see paper)
36% identity, 99% coverage: 3:319/320 of query aligns to 73:390/409 of Q10489
- Y306 (≠ W240) modified: Phosphotyrosine
- S310 (≠ F244) modified: Phosphoserine
- S312 (≠ G246) modified: Phosphoserine
Sites not aligning to the query:
- 6 modified: Phosphothreonine
P26267 Pyruvate dehydrogenase E1 component subunit alpha type I, mitochondrial; PDHA1; PDHE1-A; EC 1.2.4.1 from Ascaris suum (Pig roundworm) (Ascaris lumbricoides) (see paper)
35% identity, 98% coverage: 3:317/320 of query aligns to 52:365/396 of P26267
- S289 (≠ F244) modified: Phosphoserine
- S296 (vs. gap) modified: Phosphoserine
Q8H1Y0 Pyruvate dehydrogenase E1 component subunit alpha-2, mitochondrial; PDHE1-A; Protein IAA-CONJUGATE-RESISTANT 4; EC 1.2.4.1 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
35% identity, 98% coverage: 4:318/320 of query aligns to 59:373/393 of Q8H1Y0
- R121 (= R66) mutation to C: In iar4-1; reduced sensitivity to several IAA-amino acid conjugates.
6cerA Human pyruvate dehydrogenase complex e1 component v138m mutation (see paper)
34% identity, 99% coverage: 2:319/320 of query aligns to 28:323/342 of 6cerA
6cerE Human pyruvate dehydrogenase complex e1 component v138m mutation (see paper)
33% identity, 99% coverage: 2:319/320 of query aligns to 27:321/340 of 6cerE
3exhE Crystal structure of the pyruvate dehydrogenase (e1p) component of human pyruvate dehydrogenase complex (see paper)
33% identity, 99% coverage: 2:319/320 of query aligns to 27:312/331 of 3exhE
P12694 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; BCKDE1A; BCKDH E1-alpha; EC 1.2.4.4 from Homo sapiens (Human) (see 14 papers)
29% identity, 98% coverage: 3:317/320 of query aligns to 97:413/445 of P12694
- Y158 (≠ H65) binding
- R159 (= R66) binding ; to W: in MSUD1A; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs769688327
- Q190 (≠ G97) to K: in MSUD1A; decreased 3-methyl-2-oxobutanoate dehydrogenase activity
- S206 (≠ N113) binding
- S207 (≠ A114) binding
- P208 (≠ I115) binding
- T211 (≠ G118) binding ; to M: in MSUD1A; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs398123503
- Q212 (≠ A119) binding
- E238 (≠ D145) binding
- G239 (= G146) binding
- A240 (≠ G147) binding
- G249 (≠ A156) to S: in MSUD1A; no effect on solubility; no effect on mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs137852874
- A253 (= A160) to T: in MSUD1A; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs199599175
- A254 (≠ V161) to D: in MSUD1A; uncertain significance; loss of 3-methyl-2-oxobutanoate dehydrogenase activity
- R265 (≠ E172) binding ; to W: in MSUD1A; uncertain significance; no effect on solubility; no effect on mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs137852873
- N267 (= N174) binding ; to S: in MSUD1A; uncertain significance; no effect on solubility; no effect on mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; decreased affinity for the cofactor thiamine diphosphate; decreased 3-methyl-2-oxobutanoate dehydrogenase activity
- Y269 (= Y176) binding
- A285 (= A192) to P: in MSUD1A; no effect on solubility; no effect on mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs398123508
- G290 (= G197) to R: in MSUD1A; no effect on solubility; no effect on mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; decreased 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs137852871
- R297 (≠ T204) to H: in MSUD1A; uncertain significance; decreased affinity for the cofactor thiamine diphosphate; decreased 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs200137189
- T310 (= T217) to R: in MSUD1A; decreased solubility; changed mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs137852875
- I326 (= I233) to T: in MSUD1A; decreased 3-methyl-2-oxobutanoate dehydrogenase activity
- H336 (≠ G242) binding
- S337 (≠ H243) modified: Phosphoserine; by BCKDK; mutation to A: Substantially decreases the stability of the BCKD complex.
- S347 (≠ A253) mutation to A: Does not affect the stability of the BCKD complex.
- F409 (≠ L313) to C: in MSUD1A; decreased solubility; loss of mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs137852872
- Y413 (= Y317) to C: in MSUD1A; uncertain significance; decreased solubility; changed mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs398123508
Sites not aligning to the query:
- 1:45 modified: transit peptide, Mitochondrion
- 438 Y → N: in MSUD1A; decreased solubility; loss of mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; loss of 3-methyl-2-oxobutanoate dehydrogenase activity; dbSNP:rs137852870
Q5SLR4 2-oxoisovalerate dehydrogenase subunit alpha; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; BCKDH E1-alpha; EC 1.2.4.4 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8) (see paper)
31% identity, 84% coverage: 3:270/320 of query aligns to 33:300/367 of Q5SLR4
1umdA Branched-chain 2-oxo acid dehydrogenase (e1) from thermus thermophilus hb8 with 4-methyl-2-oxopentanoate as an intermediate (see paper)
31% identity, 84% coverage: 3:270/320 of query aligns to 28:295/362 of 1umdA
- active site: I52 (≠ Q27), S139 (≠ A114), R264 (= R239), H268 (= H243), S269 (≠ F244), Y277 (= Y251)
- binding 2-oxo-4-methylpentanoic acid: F61 (= F37), Y90 (≠ H65), S139 (≠ A114)
- binding magnesium ion: D170 (= D145), N199 (= N174), Y201 (= Y176)
- binding thiamine diphosphate: Y89 (≠ T64), Y90 (≠ H65), R91 (= R66), P140 (≠ I115), I141 (≠ V116), G169 (= G144), D170 (= D145), G171 (= G146), N199 (= N174), Y201 (= Y176), A202 (≠ G177), I203 (≠ E178), H268 (= H243)
1umcA Branched-chain 2-oxo acid dehydrogenase (e1) from thermus thermophilus hb8 with 4-methylpentanoate (see paper)
31% identity, 84% coverage: 3:270/320 of query aligns to 28:295/362 of 1umcA
- active site: I52 (≠ Q27), S139 (≠ A114), R264 (= R239), H268 (= H243), S269 (≠ F244), Y277 (= Y251)
- binding 4-methyl valeric acid: Y90 (≠ H65), H126 (= H101)
- binding magnesium ion: D170 (= D145), N199 (= N174), Y201 (= Y176)
- binding thiamine diphosphate: Y89 (≠ T64), Y90 (≠ H65), R91 (= R66), I141 (≠ V116), G169 (= G144), D170 (= D145), G171 (= G146), N199 (= N174), Y201 (= Y176), I203 (≠ E178), H268 (= H243)
1umbA Branched-chain 2-oxo acid dehydrogenase (e1) from thermus thermophilus hb8 in holo-form (see paper)
31% identity, 84% coverage: 3:270/320 of query aligns to 28:295/362 of 1umbA
- active site: I52 (≠ Q27), S139 (≠ A114), R264 (= R239), H268 (= H243), S269 (≠ F244), Y277 (= Y251)
- binding magnesium ion: D170 (= D145), N199 (= N174), Y201 (= Y176)
- binding thiamine diphosphate: Y89 (≠ T64), Y90 (≠ H65), R91 (= R66), P140 (≠ I115), I141 (≠ V116), G169 (= G144), D170 (= D145), G171 (= G146), N199 (= N174), Y201 (= Y176), A202 (≠ G177), I203 (≠ E178), H268 (= H243)
P11960 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial; Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; BCKDE1A; BCKDH E1-alpha; EC 1.2.4.4 from Rattus norvegicus (Rat) (see paper)
29% identity, 98% coverage: 3:317/320 of query aligns to 93:409/441 of P11960
- S333 (≠ H243) modified: Phosphoserine; by BCKDK
Query Sequence
>BWI76_RS14160 FitnessBrowser__Koxy:BWI76_RS14160
MMLNKQALLQAYRKMREIRTFEERLHQENTSGDIPGFIHLYTGEEAIAVGVCENLTNADF
IGSTHRGHGHCIAKGCDIHGMMAEIFGKDSGLCRGKGGSMHIADLSKGMLGANAIVGGAP
PLAIGAALTAKTLKTGNVGVSFTGDGGSNQGLVFEAINMAVVLQLPAIFIFENNGYGEGT
GHDYAVGGRDIAGRAAGFGLPAVTVDGTDFFAVYDATAEAVKRAREGGGPSVIEAKAFRW
HGHFEGDPALYRAEGEVQRLREQHDPLKIFTARVKQHISLEELAAIDAEVEALVDDAVFK
ARAAAYPAPEDLLTDVYVSY
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SitesBLAST's Database
SitesBLAST's database includes
(1) SwissProt
entries with experimentally-supported functional features;
and (2) protein structures with bound ligands, from the
BioLip database.
by Morgan Price,
Arkin group
Lawrence Berkeley National Laboratory